title: X chromosome inactivation patterns in normal and X-linked hereditary nephropathy carrier dogs.
abstract: Alport syndrome (AS) and hereditary nephropathy (HN) are glomerular nephropathies caused by mutations in the genes encoding the type IV collagens. In a mixed breed of dog, termed Navasota (NAV) dogs, X-linked hereditary nephropathy (XLHN) is caused by a 10-bp deletion in exon 9 of COL4A5. Males harboring this mutation succumb to end-stage renal disease before 18 months of age. In contrast, female carriers of this disease survive much longer, most have a normal life-span, and vary in disease progression as compared with XLHN-affected males. X chromosome inactivation (XCI) patterns have been studied in human X-linked AS carriers and some have been shown to have a high degree of skewed XCI. However, similar studies have never been reported in an animal model of this disease. Therefore, patterns of XCI were examined in XLHN-carrier NAV dogs. The variation in XCI among the 26 XLHN-carrier and seven normal female NAV dogs studied was low and only three were found to preferentially inactivate one X chromosome, all of which were XLHN-carriers. The average skewedness among all dogs was 59% and 57% among the XLHN-carriers. No significant difference in XCI was found between the two groups (P = 0.477). It is clear from these data that genotype does not seem to have an effect on inactivation; the majority of these dogs have random patterns of XCI. Highly skewed X chromosome inactivation also appears to be random, given that no difference was observed between the XLHN-carriers and normal females. Because of the apparent rarity of skewed XCI, these dogs may not be a suitable model for studying a potential correlation between this phenomenon and disease progression.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4467, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Bell
authors.forename: G E
authors.initials: GE
authors.lastname: Lees
authors.forename: K E
authors.initials: KE
authors.lastname: Murphy
mesh_terms: D000818:Animals; D001483:Base Sequence; D024141:Collagen Type IV / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000662:veterinary*; D006579:Heterozygote; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics / Q000662:veterinary*; D008297:Male; D009394:Nephritis, Hereditary / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics; D013045:Species Specificity; D049951:X Chromosome Inactivation
chemical_list: D024141:Collagen Type IV; D017931:DNA Primers; D011944:Receptors, Androgen